1. Field of the Invention
The present invention relates to an NMR probe for use in an NMR spectrometer and, more particularly, to an NMR probe permitting observation and irradiation of two nuclear species which are close in resonant frequency.
2. Description of Related Art
An NMR spectrometer is an instrument for analyzing a molecular structure by irradiating a sample placed within a static magnetic field with RF radiation, then detecting a feeble RF signal (NMR signal) emanating from the sample, and extracting information about the molecular structure contained in the signal.
FIG. 1 is a schematic block diagram of the NMR spectrometer. The spectrometer has an RF oscillator 1 producing an RF signal. The RF signal is controlled in terms of phase and amplitude by a phase controller 2 and an amplitude controller 3 and sent to a power amplifier 4.
The RF signal is amplified to an electric power necessary to excite an NMR signal by the power amplifier 4 and sent to an NMR probe 6 via a duplexer 5. Then, the signal is applied as RF pulses to the sample from a sample coil (not shown) placed within the probe 6.
After the RF irradiation, a feeble NMR signal emanating from the sample is detected by the sample coil (not shown) placed within the NMR probe 6 and sent via the duplexer 5 to a preamplifier 7, where the signal is amplified.
A receiver 8 converts the frequency of the RF NMR signal amplified by the preamplifier 7 to an audio frequency that can be converted into a digital signal. At the same time, the receiver controls the amplitude. The NMR signal converted into the audio frequency by the receiver 8 is converted into a digital signal by an analog-to-digital data converter 9 and sent to a control computer 10.
The control computer 10 controls the phase controller 2 and amplitude controller 3, Fourier-transforms the NMR signal accepted in the time domain, automatically corrects the phase of the Fourier-transformed NMR signal, and then displays the NMR signal as an NMR spectrum.
There are several kinds of RF radiation applied to the NMR probe 6. In particular, RF radiation corresponding to the resonant frequency of any one of nuclear species as shown in FIG. 2 is applied to the NMR probe. In the table of FIG. 2, the chemical symbols on the left side of each column of the table indicate the kinds of nuclei under observation, while the numerical values on the right side indicate the resonant frequencies (in MHz) of the observed nuclei in a case where they are placed within a static magnetic field of 18 tesla (T). Generally, nuclear species are classified into a group of nuclear species resonating at relatively high frequencies, such as 3H nucleus to 19F nucleus, and a group of nuclear species resonating at relatively low frequencies, such as 205Tl nucleus to 103Rh nucleus, and the two groups are treated separately. Radio frequencies of the former group are referred to as HF. Radio frequencies of the latter group are referred to as LF.
In many NMR measurements, plural nuclear species are excited at the same time and multiple resonance measurements are performed. For example, as can be seen from FIG. 2, nuclear species which are close in resonant frequency, such as 1H and 19F nuclei, are often selected as subjects to be investigated by NMR.
Generally, an NMR spectrometer is equipped with a lock mechanism for feeding variations in frequency of the NMR signal of deuterium nuclei contained in the sample back to the intensity of the static magnetic field in order to maintain constant the intensity of the static field applied to the sample to be investigated. An RF signal (hereinafter referred to as the lock signal) for this purpose is simultaneously applied to the sample coil.
FIGS. 3A and 3B show examples of an NMR probe having a singly tuned circuit that has the simplest structure and highest sensitivity (i.e., highest efficiency). In each of FIGS. 3A and 3B, a sample coil LS irradiates a sample inserted therein with an RF magnetic field and detects an NMR signal emanating from the sample after a lapse of a given time. The sample coil LS has capacitance CS. A tuning capacitor C1 is used for RF radiation HF1. A tuning variable capacitor VC1 is also used for the RF radiation HF1. A matching variable capacitor VC2 is used also for the RF radiation HF1. A tuning capacitor C3 is used for locking RF radiation (LOCK). A matching capacitor C4 is used also for the locking RF radiation.
FIG. 3A shows an NMR probe designed to cause different sample coils to resonate with the HF1 and the lock signal (LOCK). FIG. 3B shows an NMR probe designed to cause the same sample coil to resonate with the HF1 and the lock signal. In FIG. 3B, separation circuits 1 and 2 are mounted to separate the HF1 and the lock signal.
It is now assumed that a maximum sensitivity (efficiency) of the geometry of FIG. 3A is 100%. Because any member inducing interference with the resonance with the HF1 does not exist, the most ideal fundamental performance is secured.
The separation circuits are attached to the NMR probe of FIG. 3B. Generally, each separation circuit is an LC parallel resonant circuit for blocking the frequency corresponding to HF1. A dummy coil having some length may be disposed, and the frequency corresponding to HF1 may be blocked by resonating surrounding stray capacitance with a helical coil. The loss induced by the separation circuit affects the sensitivity. Because the effect is approximately 5% to 10%, it can be said that the sensitivity of the NMR probe of FIG. 3B is about 90%.
The circuits of FIGS. 3A and 3B can be tuned to the resonant frequency of 1H nucleus and to the resonant frequency of 19F nucleus. That is, the circuits can be tuned to any arbitrary frequency in the resonant frequency band HF of from 1H nucleus to 19F nucleus by appropriately adjusting the tuning variable capacitor VC1 and matching variable capacitor VC2.
The resonant frequency of such a circuit is tuned to the resonant frequency of 1H nucleus. An input voltage of 1 Vp-p (peak-to-peak voltage) is applied across the circuit. If the sensitivity of the circuit is expressed using an amplitude voltage resonating at the opposite ends of the sample coil, a sensitivity of 100% is given by about 8 Vp-p. There is a difference associated with √{square root over (f)} a between when the resonant frequency is the resonant frequency of 1H nucleus and when the resonant frequency is the resonant frequency of 19F nucleus but, generally speaking, the difference is so small that it can be neglected here. It is assumed that both kinds of nuclei produce substantially the same voltage.
It is desired to confirm that in the circuit of FIG. 3A, target voltages of the 1H nucleus resonant frequency and the 19F nucleus resonant frequency are about 8 Vp-p because this is also related to the following description. The circuit of FIG. 3B has an expectation value of about 7 Vp-p. However, both circuits of FIGS. 3A and 3B have the disadvantage that the circuit can be tuned to only one nucleus (either the 1H nucleus resonant frequency or the 19F nucleus resonant frequency) at any time.
FIGS. 4A, 4B, and 4C show an example of a multiple-tuning NMR probe capable of tuning to two nuclei of 1H and 19F at the same time. As shown in FIG. 4C, two sample coils having different diameters are disposed concentrically. A 1H tuning-and-matching circuit and a 19F tuning-and-matching circuit which are independent of each other are built for the sample coils, respectively.
Which of the inner or outer coil should be used for 1H nuclear spectroscopy or 19F nuclear spectroscopy depends on the required application. Normally, the inner coil is used for nuclear NMR spectroscopy requiring higher sensitivity. Referring to FIGS. 4A and 4B, there are two cases. In one case, Ls1=1H and Ls2=19F. In the other, Ls1=19F and Ls2=1H.
A mixture of inductive coupling and capacitive coupling is present between the two sample coils and so the sensitivity loss due to the coupling is about 15%. Therefore, the sensitivity of the circuit formed by the inner sample coil to the nuclear species is in the neighborhood of 85%. For a detector for a sample tube, for example, of 5 mm, the diameter of the inner coil is about 6 mm, while the diameter of the outer coil is about 11 mm. The ratio 6:11 of the diameters is considered as an element associated with the sensitivity.
It is expected that the sensitivity will be increased with reducing the distance between the sample tube and the sample coil. Therefore, the detection sensitivity of the circuit formed by the outer sample coil is 85×6/11≅50%. That is, in the geometry of FIG. 4A, the sensitivity of the inner coil, which is closer to the sample tube, to the nuclear species is about 85%. The sensitivity of the outer coil, which is farther from the sample tube, to the nuclear species is about 50%.
The geometry of FIG. 4A is expressed using the same concept. In a first case, lock circuitry is attached to the inner coil. In a second case, lock circuitry is attached to the outer coil.
Based on the concept described so far, in the first case, the detection sensitivity is about 85%×0.9=77%. In the second case, the detection sensitivity is about 50×0.9=45%. Therefore, in the first case, the sensitivity of the inner coil would be about 77%, while the sensitivity of the outer coil would be about 50%. In the second case, the sensitivity of the inner coil would be about 85%. The sensitivity of the outer coil would be about 45%.
In any case, the resonant frequency of 1H nucleus and the resonant frequency of 19F nucleus are very close to each other. Tuning to the resonant frequencies results in cross interference. Therefore, if one attempts to tune to the other frequency, it is difficult to make a clear tuning setting because it is hindered by crosstalk.
Consequently, tuning ranges are limited to mutually distant positions. For example, in a 400 MHz NMR spectrometer, separate tuning ranges of f(19F)=376 MHz and f(1H)=400 MHz are defined with a space of tens of MHz therebetween. In a 500 MHz NMR instrument, separate tuning ranges of f(19F)=470 MHz and f(1H)=500 MHz are defined.
When checked with resonant voltages, in the geometry of FIG. 4A, a combination of heteronuclear species of ˜8×0.85≅6.8 Vp-p (1H or 19F) and ˜8×0.5≅4 Vp-p (19F or 1H) can be anticipated. Similarly, in the geometry of FIG. 4B, a combination of heteronuclear species of ˜8×0.77≅6.2 Vp-p (1H or 19F) and ˜8×0.5≅4 Vp-p (19F or 1H) or a combination of heteronuclear species of ˜8×0.85≅6.8 Vp-p (1H or 19F) and ˜8×0.45≅3.6 Vp-p (19F or 1H) can be anticipated.
The example of FIGS. 5A and 5B is intended for compatibility of two frequencies in the same way as in the geometries of FIGS. 4A and 4B. The difference is that a circuit is built in one sample coil. In the geometry of FIGS. 5A and 5B, it is possible to tune to both 1H nucleus resonant frequency and 19F nucleus resonant frequency using a double tuning circuit equipped with generally known separation circuits. To prevent the sensitivity at the 19F nuclear resonant frequency from being deteriorated, the inductance of an inductor included in an LC parallel resonant circuit used in a separation circuit 3 is set to a minimum value.
In FIG. 5A, lock circuitry is attached to the other sample coil. In FIG. 5B, lock circuitry is attached to one sample coil. In FIG. 5A, a variable capacitor VC2 is a matching capacitor common to the 1H nucleus resonant frequency and the 19F nucleus resonant frequency and set to a position where the capacitance value is pseudo-matched at both resonant frequencies. VC1 is a tuning variable capacitor for 1H nucleus. VC3 is a tuning variable capacitor for 19F nucleus. A fixed capacitor C1 is used for tuning to an HF frequency range including the 1H nucleus resonant frequency and the 19F nucleus resonant frequency.
In this circuit, it is impossible to make complete matching to each individual frequency. As a result, a slight amount of loss arises. Since the RF radiation for the 1H nucleus is blocked by the separation circuit 3, the effects of the tuning variable capacitor VC3 are alleviated. However, a loss corresponding to the separation circuit results. In total, the sensitivity is given approximately by 100×0.9×0.9≅80%. Because the RF radiation for the 19F nucleus is affected by the whole amount of loss in the separation circuit, the sensitivity is given approximately by 100×0.9×0.6≅54%.
In FIG. 5B, lock circuitry is attached and, therefore, the RF radiation for 1H nucleus and the RF radiation for 19F nucleus suffer from the loss due to the lock circuitry. As a result of these considerations, the sensitivity to the RF radiation for 1H nucleus becomes lower than the sensitivity of the circuit of FIG. 5A and would be given approximately by 80×0.9≅72%. The sensitivity to the RF radiation for 19F nucleus would be given approximately by 54×0.9×0.9≅43%.
When checked with resonant voltages, in the geometry of FIG. 5A, results V(1H)=˜8×0.80≅6.4 Vp-p and V(19F)=8×0.54≅4.3 Vp-p can be anticipated. Similarly, in the geometry of FIG. 5B, results given by V(1H)=8×0.72=5.7 Vp-p and V(19F)=8×0.48≅3.8 Vp-p or results given by V(1H)=8×0.85≅6.8 Vp-p and V(19F)=8×0.43≅3.4 Vp-p can be anticipated.
The contents of the description provided so far are summarized in Table 1, where evaluated sensitivities are given in % and compared. The efficiencies of various methods evaluated using voltages are listed in Table 2, the methods having been used where maximum resonant voltage was about 8 Vp-p when a reference input was 1 Vp-p. The efficiencies of various methods evaluated using voltages are listed in Table 3, the methods having been used where maximum resonant voltage was about 11.5 Vp-p when a reference input was 1 Vp-p.
TABLE 1efficiency (%) evaluated using resonant voltageincompatibility of 1Hcompatibility of 1Hcompatibility of 1Hnucleus underand 19F: SW modeand 19F: SW modeand 19F: SW modeinvestigationFIG. 3AFIG. 3BFIG. 4AFIG. 4BFIG. 5AFIG. 5B1H10090855077508545807219F100905085507745855443
TABLE 2efficiency (Vp-p) evaluated using resonant voltageincompatibility of 1Hcompatibility of 1Hcompatibility of 1Hnucleus underand 19F: SW modeand 19F: SW modeand 19F: SW modeinvestigationFIG. 3AFIG. 3BFIG. 4AFIG. 4BFIG. 5AFIG. 5B1H87.26.846.246.83.66.45.819F87.246.846.23.66.84.33.4* It is assumed that resonant voltage is ~8 Vp-p at maximum efficiency when 1 Vp-p is applied.
TABLE 3efficiency (Vp-p) evaluated using resonant voltageincompatibility of 1Hcompatibility of 1Hcompatibility of 1Hnucleus underand 19F: SW modeand 19F: SW modeand 19F: SW modeinvestigationFIG. 3AFIG. 3BFIG. 4AFIG. 4BFIG. 5AFIG. 5B1H11.510.359.7755.758.95.89.85.29.28.2819F11.510.355.759.7755.88.95.29.86.24.945* It is assumed that resonant voltage is ~11.5 Vp-p at maximum efficiency when 1 Vp-p is applied.
The first means which can tune to RF radiation for 19F nucleus and RF radiation for 1H nucleus and which permits observation at the highest sensitivity is to use the probe of FIGS. 3A and 3B that shows maximum sensitivities respectively to the RF radiation for 19F nucleus and RF radiation for 1H nucleus. Sometimes, only the RF radiation for 1H nucleus is observed. In other times, only the RF radiation for 19F nucleus is observed.
In this method, however, a long time is required to observe a compound containing both 19F nucleus and 1H nucleus. Furthermore, in order to know how both nuclei are associated, it is impossible to control behaviors of the other nucleus coupled to the nucleus under observation. Consequently, it has been impossible to know the correlation between both nuclei. Hence, it may be reasonably said that the analytical apparatus does not have sufficient functions required for analysis.
Accordingly, probes capable of observing and irradiating 19F nucleus and 1H nucleus simultaneously have been offered. Each probe shown in FIGS. 4A-4C is capable of FH compatibility mode and has two ports employing two sample coils to which RF radiation for 19F nucleus and RF radiation for 1H nucleus are assigned, respectively. FIGS. 5A and 5B show a probe that is also capable of FH compatibility mode but has one port using a single sample coil to which RF radiation for 19F nucleus and RF radiation for 1H nucleus can be applied.
The geometry of FIGS. 4A-4C has the problem that when a user attempts to observe 19F nucleus and 1H nucleus both at maximum sensitivity, he must prepare two high-sensitivity probes for 19F nucleus and 1H nucleus, respectively. The geometry of FIGS. 5A and 5B has the problem that electric powers of two frequencies must be handled by one port, thus producing adverse effects, such as generation of heat by the high power of the irradiation side.
Furthermore, there is the problem that the sensitivity to 19F nucleus and the sensitivity to 1H nucleus are different greatly due to circuit configurations and because of the difference in distance between the sample tube and the coil. It has been known that both 19F nucleus and 1H nucleus are nuclear species providing high detection sensitivity per se. However, it is desired to have a probe which has high sensitivity and shows identical sensitivities to both nuclei or which is so designed that greater importance is placed on the sensitivity to 19F nucleus showing a considerably wide range of chemical shifts.